Our long-term goal is to understand the developmental and molecular basis for soma-germline interactions that influence germline proliferation and differentiation. The germ cells of most animals, including mammals, proliferate extensively during development. This proliferation is required to produce an adequate progenitor pool for adult gamete production. We are investigating how somatic signals control germline proliferation, including the role of nutrition-sensitive signaling pathways in this control. These mechanisms are not well understood and can be studied best in a whole-organism context that is amenable to genetic and molecular analysis, such as the nematode C. elegans. Despite the evolutionary distance between C. elegans and mammals, molecular pathways are largely conserved. Therefore, these studies will likely provide broadly applicable results and lend insights into general aspects of cell proliferation control in humans with implications for fertility, cancer, and stem cell biology. Recent studies from our lab implicate the distal sheath cells and the insulin-like pathway in the control of germline proliferation in C. elegans. Using molecular-genetic and biochemical techniques, as well as anatomical manipulations, we propose to identify and chacterize the relevant targets of the pathway for germline proliferation, to elucidate the role of the S6 kinase in this context, and to investigate the molecular basis for the influence of nutrition on germline proliferation. PUBLIC HEALTH RELEVANCE: Germ cells are the link from generation to generation and must proliferate to ensure fertility, and germ cell proliferation is controlled by interaction with neighboring cells and by hormones and nutrition. We study conserved molecular pathways that control germ cell proliferation. These investigations inform similar processes in humans with implications for fertility, cancer, and stem cell biology.